1. Field of the Invention
The present invention relates to a novel N.sup.6,N.sup.6 -disubstituted-cyclic adenosine-3',5'-monophosphate (referred to hereinafter as N.sup.6,N.sup.6 -disubstituted-cAMP) or a salt thereof and a novel process for preparing N.sup.6, N.sup.6 -disubstituted-cAMPs including these novel compounds. Cyclic adenosine-3',5'-monophosphate (referred to as cAMP) and its derivative have a variety of biological activities and are anticipated for their applications to biochemical agents or medicines.
2. Description of the Prior Art
It is disclosed in Eur. J. Biochem., 150, 219 (1985) that N.sup.6,N.sup.6 -disubstituted-cAMPs such as dimethyl, diethyl and diisopropyl derivatives have a cAMP-dependent protein kinase activating effect.
As a process for preparing N.sup.6,N.sup.6 -disubstituted-cAMPs, a method comprising the nucleophilic substitution of 6-chloro-9-.beta.-D-ribofuranosylpurine-3',5'-cyclic monophosphate with a dialkylamine is disclosed in Biochemistry, 11, 2704 (1972). In this method, cAMP is first deaminated by sodium nitrite to form cyclic inosine-3',5'-monophosphate, of which the 2'-OH group is protected with an acetyl group and the 6-position is chlorinated with phosphorus oxychloride, and the 6-chloro derivative is then subjected to deprotection to give 6-chloro-9-.beta.-D-ribofuranosylpurine-3',5'-cyclic monophosphate, which is reacted with diethylamine to give N.sup.6,N.sup.6 -diethyl-cAMP.
The aforementioned method requires tedious and multistep reactions and has defects such as a lowered yield due to the formation of by-products or a poorer reactivity with a longer-chain dialkylamine. This method is applied only to limited purposes because of these defects, so that it is not only unsuitable for the synthesis of a variety of N.sup.6,N.sup.6 -disubstituted-cAMP derivatives but also disadvantageous economically.
The present inventors have conducted researches for overcoming the problems on said production method. As a result, we have found that N.sup.6,N.sup.6 -disubstituted-cAMPs can be easily prepared by reacting a 2'-O-protected-cyclic adenosine-3',5'-monophosphate (referred to hereinafter as 2'-O-protected-cAMP) with an alkyl halide. They have thus prepared novel N.sup.6,N.sup.6 -disubstituted-cAMPs and found that these compounds have an excellent cardiac effect.